scholarly journals Effect of hypertension and peroxynitrite decomposition with FeTMPyP on CBF and stroke outcome

2016 ◽  
Vol 37 (4) ◽  
pp. 1276-1285 ◽  
Author(s):  
Marilyn J Cipolla ◽  
Julie G Sweet ◽  
Siu-Lung Chan
Keyword(s):  
Vascular Function ◽  
Infarct Volume ◽  
Myogenic Tone ◽  
Sham Operation ◽  
Stroke Outcome ◽  
Perfusion Deficit ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Vessel Resistance ◽  
Hydrogen Clearance

We investigated the effect of peroxynitrite decomposition catalyst FeTMPyP treatment on perfusion deficit, vascular function and stroke outcome in Wistar ( n = 26) and spontaneously hypertensive rats stroke-prone (SHRSP; n = 26) that underwent tMCAO for 2 h or Sham operation. Peri-infarct CBF was measured by hydrogen clearance in the absence or presence of FeTMPyP (10 mg/kg, i.v.) or vehicle 10 min before reperfusion. Myogenic tone of parenchymal arterioles (PAs) was measured as an indication of small vessel resistance (SVR). Baseline CBF was similar between Wistar and SHRSP (114 ± 12 vs. 132 ± 9 mL/100 g/min); however, MCAO caused greater perfusion deficit in SHRSP (24 ± 6 vs. 7 ± 1 mL/100 g/min; p < 0.05) and increased infarct volume by TTC (12 ± 6 vs. 32 ± 2%; p < 0.05). Reperfusion CBF was decreased from baseline in both SHRSP and Wistar (54 ± 16 and 46 ± 19 mL/100 g/min; p < 0.05), suggesting increased infarction in SHRSP was related to greater perfusion deficit. PAs from SHRSP had increased tone vs. Wistar that was enhanced after tMCAO. FeTMPyP treatment did not affect CBF during ischemia or reperfusion, or tone of PAs, but decreased the incidence of hemorrhage in SHRSP by 50%. Thus, increased tone in PAs from SHRSP could increase perfusion deficit during MCAO that was not alleviated by FeTMPyP.

Abstract 62: Sanguinate TM Opens Collaterals, Improves Reperfusion and Decreases Infarct in Hypertensive Rats

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Marilyn Cipolla ◽  
Italo Linfante ◽  
Abe Abuchowski ◽  
Ronald Jubin ◽  
Siu-Lung Chan
Keyword(s):  
Time Window ◽  
Infarct Volume ◽  
Blood Gases ◽  
Artery Occlusion ◽  
Stroke Outcome ◽  
Hypertensive Rats ◽  
Triphenyltetrazolium Chloride ◽  
Spontaneously Hypertensive ◽  
Normal Ranges ◽  
Cerebral Artery Occlusion

Background: The PEGylated cell-free carboxyhemoglobin gas exchanger Sanguinate TM (SG) has multiple beneficial actions that may improve stroke outcome including anti-inflammatory, vasodilatory and oxygen delivery capacity. We investigated the ability of SG to improve infarction in spontaneously hypertensive rats (SHR) that are known to have vasoconstricted pial collaterals and poor stroke outcome. Methods: SHR were treated IV with SG (8 ml/kg; n=8) or vehicle (Lactated Ringer’s; n=6) plus tPA (0.9 mg/ml) after 30 min of proximal middle cerebral artery occlusion (MCAO) by filament occlusion. Pial collateral and reperfusion flow were measured for 2 hrs of occlusion and 2 hrs reperfusion using dual laser Doppler probes in the core (Bregma -2mm, lateral +4mm) and collateral (Bregma +2mm, lateral +3mm) territories. Collateral openings (number and duration (min)) were assessed off cerebral blood flow (CBF) tracings, defined as independent of changes in blood pressure (Fig. 1; arrows show openings). Infarction was measured using triphenyltetrazolium chloride (TTC). Animals were anesthetized with chloral hydrate and ventilated to maintain blood gases within normal ranges. Results: Vehicle-treated SHR had incomplete reperfusion and poor collaterals that was improved by SG. During MCAO, SG increased the number of collateral openings from 1.0±0.8 to 3.1±0.8 (p=0.03) and duration of openings from 6.0±5.8 to 35.4±9.8 min (p=0.04; Fig. 2). Reperfusion CBF was -43±6% of baseline in vehicle-treated, but only -7±19% of baseline in SG-treated animals. Improved collateral and reperfusion flow with SG was associated with decreased infarct volume vs. vehicle (28.8±3.2% vs. 18.8±2.3%; p<0.05). The presence of tPA had no effect in either group. Conclusions: Smaller infarction with early SG treatment may be related to its ability to open constricted collaterals in SHR and improve reperfusion. Thus, SG may be able to extend the time window for endovascular or tPA treatment.

Effects of high-cholesterol and atherogenic diets on vascular relaxation in spontaneously hypertensive rats

1997 ◽  
Vol 273 (2) ◽  
pp. H647-H654 ◽  
Author(s):  
M. Cappelli-Bigazzi ◽  
S. Rubattu ◽  
C. Battaglia ◽  
R. Russo ◽  
I. Enea ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Function ◽  
Spontaneously Hypertensive Rats ◽  
Vascular Reactivity ◽  
Male Rats ◽  
Standard Diet ◽  
High Cholesterol ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Endothelium Dependent Relaxation

Hypercholesterolemia is associated with more rapid development of atherosclerosis, and hypertension is frequently associated with abnormal vascular function. Therefore, to investigate the role of hypercholesterolemia and hypertension on vascular function, we studied three groups of male rats (aged 6 wk): normotensive Wistar-Kyoto rats (WKY) as a control group and spontaneously hypertensive rats (SHR) receiving either standard diet (SD; SHR-SD) or high-cholesterol (1%) diet (ChD; SHR-ChD). Vascular reactivity was tested on isolated aortic rings at 4 wk and at 3 and 6 mo of diet. At 3 mo, endothelium-dependent relaxation to acetylcholine (ACh) and ADP was significantly reduced in SHR-ChD but not in SHR-SD compared with WKY. At 6 mo, relaxations to ACh were further impaired in both SHR groups compared with WKY. Endothelium-independent vasodilation to nitroglycerin (NTG) was not different in the three groups of animals throughout 6 mo of diet. In additional experiments, we evaluated vascular reactivity in rats fed with ChD enriched with an excess of vitamin D [atherogenic diet (AD)] capable of producing vascular atherosclerotic lesions. In particular, we studied three additional groups of WKY and SHR rats fed with SD, AD, or AD plus a nonhypotensive dose of the calcium antagonist nitrendipine (Nit). Vasodilation to ACh and ADP was significantly blunted in WKY-AD compared with WKY-SD, whereas it was partially improved in WKY-Nit. There were no differences in endothelium-independent relaxation to NTG in the three WKY groups. In contrast, SHR-AD showed a marked reduction of endothelium-dependent and -independent vasodilation, but only endothelium-dependent vasodilation was preserved by addition of Nit to the diet. These data suggest that the development of vascular dysfunction in rat genetic hypertension is accelerated by ChD, in absence of detectable vascular lesions. Our study also shows that AD alters both vascular smooth muscle and endothelium-dependent relaxation. Low doses of Nit partially preserve endothelium-dependent vasodilation but do not affect the impairment of smooth muscle function in these rats.

835 AGE-RELATED CHANGES IN VASCULAR FUNCTION OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

2012 ◽  
Vol 30 ◽  
pp. e243
Author(s):  
Angelika Puzserova ◽  
Veronika Ilovska ◽  
Peter Balis ◽  
Peter Slezak ◽  
Natalia Sestakova ◽  
...  
Keyword(s):  
Vascular Function ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Age Related ◽  
Age Related Changes

scholarly journals Rapamycin Induces an eNOS (Endothelial Nitric Oxide Synthase) Dependent Increase in Brain Collateral Perfusion in Wistar and Spontaneously Hypertensive Rats

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2834-2843
Author(s):  
Daniel J. Beard ◽  
Zhaojin Li ◽  
Anna M. Schneider ◽  
Yvonne Couch ◽  
Marilyn J. Cipolla ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Spontaneously Hypertensive Rats ◽  
Infarct Volume ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background and Purpose: Rapamycin is a clinically approved mammalian target of rapamycin inhibitor that has been shown to be neuroprotective in animal models of stroke. However, the mechanism of rapamycin-induced neuroprotection is still being explored. Our aims were to determine if rapamycin improved leptomeningeal collateral perfusion, to determine if this is through eNOS (endothelial nitric oxide synthase)-mediated vessel dilation and to determine if rapamycin increases immediate postreperfusion blood flow. Methods: Wistar and spontaneously hypertensive rats (≈14 weeks old, n=22 and n=15, respectively) were subjected to ischemia by middle cerebral artery occlusion (90 and 120 minutes, respectively) with or without treatment with rapamycin at 30-minute poststroke. Changes in middle cerebral artery and collateral perfusion territories were measured by dual-site laser Doppler. Reactivity to rapamycin was studied using isolated and pressurized leptomeningeal anastomoses. Brain injury was measured histologically or with triphenyltetrazolium chloride staining. Results: In Wistar rats, rapamycin increased collateral perfusion (43±17%), increased reperfusion cerebral blood flow (16±8%) and significantly reduced infarct volume (35±6 versus 63±8 mm 3 , P <0.05). Rapamycin dilated leptomeningeal anastomoses by 80±9%, which was abolished by nitric oxide synthase inhibition. In spontaneously hypertensive rats, rapamycin increased collateral perfusion by 32±25%, reperfusion cerebral blood flow by 44±16%, without reducing acute infarct volume 2 hours postreperfusion. Reperfusion cerebral blood flow was a stronger predictor of brain damage than collateral perfusion in both Wistar and spontaneously hypertensive rats. Conclusions: Rapamycin increased collateral perfusion and reperfusion cerebral blood flow in both Wistar and comorbid spontaneously hypertensive rats that appeared to be mediated by enhancing eNOS activation. These findings suggest that rapamycin may be an effective acute therapy for increasing collateral flow and as an adjunct therapy to thrombolysis or thrombectomy to improve reperfusion blood flow.

scholarly journals Beneficial Effects of Spirulina Aqueous Extract on Vasodilator Function of Arteries from Hypertensive Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Diva M. Villalpando ◽  
Carlos M. Verdasco-Martín ◽  
Ignacio Plaza ◽  
Juan Gómez-Rivas ◽  
Fermín R de Bethencourt ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Aqueous Extract ◽  
Vascular Function ◽  
Katp Channel ◽  
Premature Death ◽  
The Other ◽  
Hypertensive Rats ◽  
No Donor ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects

Hypertension is a multifactorial disorder considered one of the major causes of premature death worldwide. This pathology is associated with vascular functional/structural alterations in which nitric oxide (NO) and oxygen reactive species participate. On the other hand, the use of microalgae extracts in the treatment of cardiovascular diseases is increasing. Based on the antioxidant and antihypertensive properties of Spirulina, this study aims to investigate the effect of an aqueous extract of Spirulina on the vasodilator function of the aorta from spontaneously hypertensive rats (SHR), analyzing the functional role of NO. For this, aortic segments from male SHR were divided into two groups, one control and the other exposed to an Spirulina aqueous extract (0.1% w/v, for 3 hours), to analyze (i) the production of NO, superoxide anion, and hydrogen peroxide; (ii) the vasodilator response induced by acetylcholine (ACh), by the NO donor and sodium nitroprusside (SNP), and by the KATP channel opener and pinacidil; and (iii) the expression of the p-Akt, p-eNOS, and HO-1 proteins. The results showed that the aqueous Spirulina extract (i) increased the production of NO, did not significantly modify that of superoxide, while decreased that of hydrogen peroxide; (ii) increased the vasodilatory responses induced by ACh, NPS, and pinacidil; and (iii) increased the expression of p-Akt and HO-1. These results suggest that incubation with the aqueous Spirulina extract improves the vascular function of arteries from SHR by increasing the release/bioavailability/function of NO. Increased KATP channel activation and expression of pAkt and HO-1 appear to be participating in these actions.

Myogenic tone in mesenteric arteries from spontaneously hypertensive rats

1996 ◽  
Vol 270 (1) ◽  
pp. H1-H6 ◽  
Author(s):  
A. S. Izzard ◽  
S. J. Bund ◽  
A. M. Heagerty
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Mesenteric Arteries ◽  
Myogenic Tone ◽  
Hypertensive Rats ◽  
Tension Development ◽  
Spontaneously Hypertensive ◽  
Wide Pressure Range ◽  
Wistar Kyoto ◽  
Wide Pressure

To investigate myogenic tone during the developmental and established phases of hypertension, segments of distal (6th order) mesenteric arteries from spontaneously hypertensive rats (SHR) at 5 and 20 wk were isolated and pressurized in vitro and compared with vessels from age-matched Wistar-Kyoto (WKY) control animals. At 5 wk, tone was significantly enhanced in the SHR. At 20 wk tone was no longer significantly increased over a wide pressure range, although arteries from the SHR were able to maintain diameter at all pressures studied, whereas vessels from the WKY exhibited forced distension at 180 and 200 mmHg. From the relative slope of the pressure-diameter relationship (myogenic index), no increase in peak myogenic responsiveness was observed in arteries from the SHR at either time point. Passive lumen diameters were significantly decreased in arteries from SHR at both time points. From the total and passive midwall circumference-tension relationships, total tension was observed at a reduced midwall circumference in the SHR, but increased absolute levels of total tension were not observed. The normalized midwall circumference-tension relationships in the two strains revealed increased total tension due to active tension development at a reduced normalized circumference at 5 wk in the SHR. At 20 wk the normalized midwall circumference-tension relationships in the two strains were identical. These results demonstrate that myogenic tone in mesenteric arteries is enhanced during the development of hypertension but not when it is established, except at high intraluminal pressures.

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